Current Enzyme Inhibition - Current Issue

Indole, a bicyclic heterocyclic compound consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring, is a versatile structural motif in medicinal chemistry. Its unique structure allows it to interact with various biological targets, making it a valuable scaffold in drug design. Moreover, indole derivatives have been widely explored for their pharmacological activities, including antibacterial, antipsychotic, anticholinergic, anti-inflammatory, anticancer, antiviral, and antifungal properties.

A novel series of 3-(2-(1H-indol-2-yl)phenyl)-2-(substituted phenyl)-3,4-dihydroimidazo [4,5-b]indoles (4a–4j) was synthesized via condensation of 2-(o-aminophenyl)indole with aromatic aldehydes in ethanol. Structures were confirmed using FT-IR and ¹H-NMR spectroscopy. The compounds were evaluated for antibacterial and antifungal activities, supported by molecular docking studies targeting Lanosterol 14-α demethylase and DNA Gyrase B.

Five compounds (4g, 4j, 4i, 4c, and 4b) showed significant antibacterial action against gram-positive B. subitilis and gram-negative E. coli and antifungal activity against C. albicans and A. niger. Molecular docking studies, performed in comparison with the standard drugs chloramphenicol and ketoconazole, revealed how the synthesized ligands bind within the active pockets. The results showed that compound 4b exhibits significant antibacterial activity, while compound 4c demonstrates good antifungal activity.

This study successfully synthesized a novel series of indole-based dihydroimidazo[4,5-b]indoles (4a–4j) with confirmed structures via FT-IR and ¹H-NMR. Compounds 4b and 4c exhibited significant antibacterial and antifungal activities, respectively. Molecular docking revealed strong binding affinities with DNA Gyrase B and Lanosterol 14-α demethylase, supporting the observed bioactivity. These findings suggest promising potential for further antimicrobial drug development.

This study highlights the unique structures and potent antimicrobial activities of the synthesized compounds, showing their strong potential as novel antibacterial and antifungal agents with valuable therapeutic applications.

Xanthones, also known as dibenzo-γ-pyrone or 9H-xanthen-9-ones, constitute an essential group of oxygenated heterocycles that possess a dibenzo-pyrone structure having the chemical formula C13H8O2. These compounds have generated significant interest due to their high taxonomic relevance and pharmacological characteristics. Xanthone and its derivatives are cytotoxic medications due to their planar structure and capacity to intercalate with Deoxyribonucleic acid (DNA). As a DNA intercalator, xanthone extraction and synthesis have become popular in cytotoxic research.

We developed a series of novel xanthone derivatives via conventional synthesis and we then assessed their anticancer efficacy against the A549 human lung cancer cell line utilizing the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Furthermore, we conducted a docking study using a receptor with the Protein Data Bank (PDB) ID: IZXM to validate the anticancer activity of the synthesized compounds in silico.

Drug likeliness and molecular docking studies confirmed the biopotential and anticancer effectiveness of novel human DNA topoisomerase IIα inhibitors. Our in vitro anticancer activity results indicated that synthesized compound 5a had the lowest half-maximal inhibitory concentration (IC50) value and a higher cytotoxicity activity.

The newly synthesized xanthone derivatives showed promising anticancer potential, particularly compound 5a, which exhibited favorable in silico properties.

The study concluded that synthesizing new xanthone derivatives and evaluating their cytotoxic activity showed promising potency in compound 5a as an anticancer candidate. The synthesized compounds have silico drug-relevant properties, which ensure their potential leads for future drug discovery studies.

The present study investigates the structural and functional attributes of HCN synthase, known for its role in metals recovery from natural and secondary sources and gaining attention in the field of biohydrometallurgy.

The nucleotide sequences of 23 bacterial strains in reference to Pseudomonas aeruginosa were procured from the UniPROT and were subjected to analyses using SWISS-MODEL, PDBsum, ESBRI, MEME, InterProScan, and MEGA X.

Multiple sequence alignment showed a total of sixteen 100% conserved positions in the aligned region. The physico-chemical characteristics showed molecular weight between 39.24–46.79 kDa, pI range of 4.99–10.43, instability index from 26.69–50.66, and aliphatic index ranging from 83.07-101.59. The amino acid contents - Leucine (10.3%), Alanine (9.8%), Glycine (9.3%), Valine (6.8%), and Glutamic acid (6.3%) were found predominantly. The secondary structure revealed that the enzyme is dominated by 37.44% of amino acid residues in random coils, 36.97% in alpha-helices and 17.50% in extended sheets.

The secondary structure prediction revealed that the enzyme consists of twelve α-helices that interact through nineteen helix-helix interactions along with twenty-three beta strands and three gamma turns. Moreover, the tertiary structure prediction showed the structural stability, consistency, and reliability of the HCN synthase protein. In addition, functional analysis unveiled the transmembrane regions, protein-protein interactions, post-translational modifications, and phosphorylation sites of the protein.

Fundamentally, the study uncovered valuable perspectives on a stable and consistent structure of HCN synthase, providing significant insights into its characteristics.

Thus, the present study improves the understanding of HCN synthase and offers a foundation for future research.

Alzheimer’s disease (AD) is a neurodegenerative disorder marked by memory loss and cognitive decline, primarily linked to the excessive breakdown of acetylcholine by the enzyme Acetylcholinesterase (AChE), which impairs neurotransmission. Current research is exploring plant-derived compounds that inhibit AChE, offering a potential therapeutic approach for AD.

This study aimed to screen indigenous medicinal plants and their parts for acetylcholinesterase inhibitory activity.

Eleven medicinal plants from the Rajasthan state of India were collected. Twenty-six plant extracts were prepared using methanol. AChE inhibitory activity was assessed using a spectrophotometer and HPTLC bioassay based on Ellman's method. Experiments were conducted in triplicate.

TLC bioautographic (qualitative) (with the concentration of methanolic extract being 10mg/ml and inhibition time approximately 15-20 minutes) and spectrophotometric (quantitative) (with the concentration of methanolic extract being 1mg/ml and inhibition time approximately 2-3 minutes) methods revealed that extracts from nine of the eleven plant species exhibited AChE inhibitory activity. Specifically, the fruit extract of Cucumis callosus Cogn exhibited maximum activity (73.72 ± 3.93%), and the flower extract of Trifolium alexandrinum L. demonstrated minimum (19.78 ± 3.09%) acetylcholinesterase inhibitory activity.

AChE inhibitors derived from plant extracts have gained significant attention due to their potential in managing Alzheimer’s disease. Natural AChE inhibitors are often associated with fewer side effects compared to synthetic drugs, making them promising candidates for therapeutic development. Continued exploration of plant-based inhibitors could lead to safer and more effective treatments for cognitive decline.

In conclusion, fourteen extracts from nine plant species exhibited notable cholinesterase inhibition, suggesting their potential as candidates for further research.

Ficus palmata is a herbaceous perennial plant belonging to the family Moraceae. It is used in various diseases, e.g., gastrointestinal disorders, tumours, hypoglycaemia, ulcers, hyperlipidaemia, diabetes, and fungal infections.

The fruit of the Ficus palmata plant was extracted. The total phenolic and total flavonoid content were determined. Following column chromatography, phytoconstituents were isolated and identified by mass spectroscopy, FTIR, and NMR. The antioxidant activity of phytoconstituents was evaluated, and molecular docking studies were performed against the H⁺K⁺-ATPase enzyme and H2 Receptor.

The extract from Ficus palmata yielded rich in flavonoids and phenolic content. Isolation of compounds was done and characterized to be rutin and luteolin. The further evaluation of the antioxidant activity of compounds demonstrated significant activity with an IC50 value indicating strong free radical scavenging activity. Molecular docking studies were performed against the H⁺K⁺-ATPase enzyme and H2 Receptor, revealing that both compounds exhibit high binding affinity and favourable interactions with key sites.

The study revealed that Ficus palmata fruit extract is a rich source of flavonoids and phenolics, notably rutin and luteolin. These compounds demonstrated strong antioxidant activity through various free radical scavenging assays. Molecular docking suggested their potential as inhibitors of the H⁺K⁺-ATPase enzyme and H2 receptor, indicating antiulcer potential. These findings support the therapeutic relevance of Ficus palmata in oxidative stress-related gastric disorders.

The findings suggest that the isolated compounds rutin and luteolin possess potential antioxidant activity and could be a potential therapeutic target for the H⁺K⁺-ATPase enzyme and H2 Receptor.